OBJECTIVE: To explore the molecular mechanism of brain protection against convulsive brain damage in premature brains by observing the changes of apoptotic-regulating genes of bcl-2 and c-Jun expression in the hippocampus in Wistar rats with different ages after status convulsion (SC). METHODS: SC was induced in infant Wistar rats (IRs) and adult Wistar rats (ARs) by intraperitoneal injection of lithium-pilocarpine. The rats were sacrificed at 3 hrs, 6 hrs, 12 hrs, 1 day, 3 days and 7 days after SC (n=8). Bcl-2 and c-Jun protein and mRNA levels were measured using immunocytochemistry, RT-PCR and in situ hybridization. RESULTS: c-Jun protein levels increased significantly at 3 hrs and reached the peak at 6 hrs after SC in both IRs and ARs compared to those in the normal control group (P<0.01). c-Jun protein levels started to decrease 12 hrs after SC in both IRs and ARs. The expression of c-Jun protein in IRs returned to the basal level 1 day after SC, while remained higher in ARs than in the normal control group by 7 days after SC. The expression of c-Jun protein in ARs was much higher than that in IRs from 6 hrs to 7 days after SC (P<0.05). c-Jun mRNA level was in parallel with the protein level as mentioned in IRs and ARs after SC. There were no changes observed in both bcl-2 protein and bcl-2 mRNA levels after SC in IRs and ARs. CONCLUSIONS: SC may induce an up-regulation of proapoptotic gene c-Jun in the hippocampus after SC, with a less strong extent and shorter duration in IRs compared to that in ARs. This might be one mechanism of brain protection against convulsive brain damage in IRs. The expression of bcl-2 remains unchanged after SC and is not affected by age in both IRs and ARs.
Key words
Status convulsivus /
c-Jun /
Bcl-2 /
Rats
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
［1］蒋莉，蔡方成，张晓萍. 大鼠不同成熟期大脑对持续惊厥的耐受性［J］.中华儿科杂志，2002，40（7）：429-432.
［2］Moshé SL. Brain injury with prolonged seizures in children adults［J］. J Child Neurol, 1998, 13(Suppl 1): S3-S6.
［3］胡越，蒋莉，李欣，张晓萍. 持续惊厥后影响海马神经元凋亡的相关因素［J］. 中华神经科杂志，2006，39（1）：36-38.
［4］胡越，蒋莉. 有效控制氯化锂匹罗卡品诱发惊厥持续状态发作的实验研究［J］. 儿科药学杂志，2003，9(4): 5-8.
［5］Setkowicz Z, Janeczko K. Long-term changes in susceptibility to pilocarpine-induced status epilepticus following neocortical injuries in the rat at different developmental stages［J］.Epilepsy Res, 2003, 53(3): 216-224.
［6］苑爱云，蒋莉，李欣. 年龄和惊厥持续时间对持续惊厥发作后海马细胞色素C释放的影响［J］. 第四军医大学学报，2006, 27（7）:577-579.
［7］Eilers A, Whitfield J, Vekrellis K, Neame SJ, Shah B, Ham J. c-Jun and Bax: regulators of programmed cell death in developing neurons［J］. Biochem Soc Trans, 1999, 27(6): 790-797.
［8］Szot P, White SS, Shen DD, Anderson GD . Valproic acid, but not lamotrigine, suppresses seizure-induced c-fos and c-Jun mRNA expression［J］. Brain Res Mol Brain Res, 2005, 135(1-2): 285-289.
［9］Storey TW, Rho JM, White SS, Sankar R, Szot P. Age-dependent differences in flurothyl-induced c-fos and c-Jun mRNA expression in the mouse brain［J］. Dev Neurosci, 2002, 24(4): 294-299.
［10］Gross A. Bc1-2 proteins: regulators of the mitochondrial apoptotic program［J］. IUBMB Life, 2001, 52(3-5): 231-236.
［11］Henshall DC, Simon RP. Epilepsy and apoptosis pathways［J］. J Cereb Blood Flow Metab, 2005, 25(12): 1557-1572.
［12］安仁哲，尹永日，金春姬，金政，李根焕.癫癎发作诱发的程序性细胞死亡机制与神经细胞坏死的关系［J］.中华儿科杂志，2003，41(4): 290-292.
［13］Ferrei I. Cell signaling in the epileptic hippocampus［J］. Rev, 2002, 34(6): 544-550.
［14］蒋莉，蔡方成，张晓萍. 未成熟大脑对惊厥性脑损伤耐受性的分子生物学机理研究［J］.重庆医科大学学报，2005，30（5）：640-643.
PDF(1047 KB)
